Tagrisso Significantly Extends Disease-Free Survival in Early-Stage EGFR-Mutated NSCLC Regardless of Prior Adjuvant Chemotherapy

January 29, 2021/BioValleyBIOON/--AstraZeneca(AstraZeneca) recently at the 21st World Conference on Lung Cancer (WCLC) 2020, hosted online by the International Association for the Study of Lung CancerConferenceThe results of an exploratory analysis of the Phase 3 ADAURA study evaluating Tagrisso (Chinese brand name: Taisisha; generic name: osimertinib) for the treatment of lung cancer were published. The data showed that,In patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC), adjuvant therapy with Tagrisso significantly prolonged disease-free survival (DFS), regardless of prior adjuvant chemotherapy or disease stage.In the adjuvant therapy announced last year, Tagrisso achieved unprecedented DFS outcomes.

In this exploratory analysis of the entire study population,Tagrisso adjuvant therapy reduced the risk of disease recurrence or death by 84% in patients who had previously received adjuvant chemotherapy.（HR=0.16，95%CI:0.10-0.26）、Reduced the risk of disease recurrence or death by 77% in patients who had not previously received adjuvant chemotherapy（HR=0.23；95%CI:0.13-0.40）。The benefits of DFS are similar across all stages of the disease.

Furthermore, a separate exploratory post-hoc analysis of patient-reported outcomes from the ADAURA study demonstrated that patients treated with Tagrisso maintained their quality of life, with no clinically meaningful differences observed between the Tagrisso and placebo groups in terms of physical or mental health.

Professor Wu Yilong, Principal Investigator of the Phase III ADAURA trial and Director of the Lung Cancer Institute at Guangdong Provincial People’s Hospital, stated: “The substantial disease-free survival benefit observed in patients in the ADAURA study has already supported the role of Tagrisso as a pioneering adjuvant therapy for EGFR-mutated non-small cell lung cancer. This latest analysis demonstrates that the magnitude of this benefit is consistent regardless of prior adjuvant chemotherapy use and across disease stages, further reinforcing the critical role of Tagrisso in this treatment setting.”

AstraZenecaTumorDave Fredrickson, Executive Vice President of the Business Unit, stated, “These new data demonstrate that Tagrisso provides transformative benefits independent of prior chemotherapy, preventing lung cancer recurrence while allowing patients to maintain their quality of life. Following the recent approval of Tagrisso for adjuvant therapy in the United States, we continue to urgently collaborate with regulatory authorities worldwide to make this new standard of care available to patients with early-stage lung cancer.”

ADAURA is a randomized, double-blind, global, placebo-controlled Phase III study conducted in 682 patients with early-stage (Stage IB/II/IIIA) EGFR-mutant non-small cell lung cancer (EGFRm-NSCLC) who had receivedTumorComplete resection and optional standard postoperative adjuvant chemotherapy were employed to evaluate the efficacy and safety of Tagrisso in the adjuvant setting. In the study, patients in the experimental arm received Tagrisso 80 mg orally once daily for three years or until disease recurrence. The study was conducted across more than 200 clinical centers in over 20 countries, including those in Europe, South America, Asia, and the Middle East. The primary endpoint was disease-free survival (DFS) in patients with stage II/IIIA disease, and the key secondary endpoint was DFS in patients with stage IB/II/IIIA disease.

The primary results of this study were published in The New England Journal of Medicine in September 2020. The results showed that: (1) In patients with stage II and IIIA EGFRm NSCLC, adjuvant therapy with Tagrisso reduced the risk of disease recurrence or death by 83% (HR=0.17; 95% CI: 0.12–0.23; p<0.0001). (2) In the overall study population (patients with stage IB/II/IIIA), adjuvant therapy with Tagrisso reduced the risk of disease recurrence or death by 80% (HR=0.20; 95% CI: 0.15, 0.27; p<0.0001). As demonstrated in the pre-specified exploratory analysis, there was a clinically meaningful improvement in central nervous system (CNS) DFS compared with placebo.

Based on the unprecedented efficacy results from the ADAURA study, the United StatesFDAApproved Tagrisso in December 2020 as an adjuvant (postoperative) therapy for the treatment of patients who have undergone complete resection with curative intentTumorAdult patients with early-stage (Stage IB/II/IIIA) EGFR-mutated NSCLC undergoing resection.

Tagrisso is a third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) capable of overcoming resistance to first- and second-generation EGFR-TKIs, including Roche/Astellas Tarceva, AstraZeneca Iressa, and Boehringer Ingelheim Gilotrif (afatinib).

Tagrisso inhibits EGFR sensitizing mutations and the EGFR T790M resistance mutation, demonstrating clinical activity against central nervous system metastases. To date, Tagrisso 40 mg and 80 mg once-daily oral tablets have been approved in multiple countries (including the United States, Japan, China, and the European Union) for the first-line treatment of EGFR-mutated advanced NSCLC, and in multiple countries (including the United States, Japan, China, and the European Union) for the second-line treatment of patients with EGFR T790M mutation-positive advanced NSCLC. Furthermore, in the United States and several other countries, Tagrisso is also approved: as an adjuvant (postoperative) therapy for the treatment of patients who have undergone complete resection with curative intentTumorAdult patients with early-stage (Stage IB/II/IIIA) EGFR-mutated NSCLC undergoing resection.

Currently, AstraZeneca is developing Tagrisso for locally advanced unresectable disease (LAURA study), in combination with chemotherapy for metastatic disease (FLAURA2), and in combination with potential new drugs to address resistance to EGFR TKIs (SAVANNAH study, ORCHARD study). (Bioon.com)

Original Source: Tagrisso Extended Disease-Free Survival Regardless of Prior Adjuvant Chemotherapy in Early-Stage EGFR-Mutated Lung Cancer